Chronic tooth pulp inflammation induces persistent expression of phosphorylated ERK (pERK) and phosphorylated p38 (pp38) in trigeminal subnucleus caudalis

Autor: M A, Worsley, C E, Allen, A, Billinton, A E, King, F M, Boissonade
Rok vydání: 2013
Předmět:
Photomicrography
endocrine system
chronic inflammation
trigeminal nucleus
AOI
area of interest
PBS
phosphate-buffered saline
Cell Count
CFA
complete Freund’s adjuvant
p38 Mitogen-Activated Protein Kinases
NeuN
neuron-specific nuclear protein
Article
Trigeminal Caudal Nucleus
JOR
Jaw-opening reflex
pERK
ERK
extracellular signal-regulated kinase
NDS
normal donkey serum
Vc
trigeminal subnucleus caudalis
Physical Stimulation
Animals
Cy3
indocarbocyanine
pain
Phosphorylation
p38
p38 MAPK
Extracellular Signal-Regulated MAP Kinases
Dental Pulp
ANOVA
analysis of variance
PBST
phosphate-buffered saline containing Triton-X
Neurons
Ferrets
GFAP
glial fibrillary acidic protein
Pulpitis
pp38
Immunohistochemistry
MAPK
NGS
normal goat serum
Disease Models
Animal
EMG
electromyogram
Microscopy
Fluorescence
pp38
phosphorylated p38
Astrocytes
Female
FITC
fluorescein isothiocyanate
Chronic Pain
pERK
phosphorylated ERK
Proto-Oncogene Proteins c-fos
MAPK
mitogen-activated protein kinase
Zdroj: Neuroscience
ISSN: 1873-7544
Popis: Highlights • Chronic inflammation of tooth pulp activates pERK and pp38 in the trigeminal nucleus • Activation is persistent and bilateral, and further increased by acute stimulation • This altered signaling may be relevant in the development of chronic pulpitic pain • pERK and pp38 are more sensitive markers of central change than Fos expression • Sequential activation in different cell types may be linked to pain progression
Background Extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase are transiently phosphorylated (activated) in the spinal cord and trigeminal nucleus by acute noxious stimuli. Acute stimulation of dental pulp induces short-lived ERK activation in trigeminal subnucleus caudalis (Vc), and p38 inhibition attenuates short-term sensitization in Vc induced by acute pulpal stimulation. We have developed a model to study central changes following chronic inflammation of dental pulp that induces long-term sensitization. Here, we examine the effects of chronic inflammation and acute stimulation on the expression of phosphorylated ERK (pERK), phosphorylated p38 (pp38) and Fos in Vc. Results Chronic inflammation alone induced bilateral expression of pERK and pp38 in Vc, but did not induce Fos expression. Stimulation of both non-inflamed and inflamed pulps significantly increased pERK and pp38 bilaterally; expression was greatest in inflamed, stimulated animals, and was similar following 10-min and 60-min stimulation. Stimulation for 60 min, but not 10 min, induced Fos in ipsilateral Vc; Fos expression was significantly greater in inflamed, stimulated animals. pERK was present in both neurons and astrocytes; pp38 was present in neurons and other non-neuronal, non-astrocytic cell types. Conclusions This study provides the first demonstration that chronic inflammation of tooth pulp induces persistent bilateral activation of ERK and p38 within Vc, and that this activation is further increased by acute stimulation. This altered activity in intracellular signaling is likely to be linked to the sensitization that is seen in our animal model and in patients with pulpitis. Our data indicate that pERK and pp38 are more accurate markers of central change than Fos expression. In our model, localization of pERK and pp38 within specific cell types differs from that seen following acute stimulation. This may indicate specific roles for different cell types in the induction and maintenance of pulpitic and other types of pain.
Databáze: OpenAIRE
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